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In Case You Missed It: COVID
Suicidality jumped in Israel during spring COVID-19 lockdown
Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.
He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.
It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.
The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.
“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.
The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.
“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.
The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.
Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.
Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.
“ You can kill your grandfather by coughing,” Dr. Zalsman said.
Older people also seek help
A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.
The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.
“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.
Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.
SOURCE: Zalsman G. ECNP 2020, Session TP.06.
Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.
He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.
It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.
The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.
“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.
The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.
“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.
The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.
Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.
Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.
“ You can kill your grandfather by coughing,” Dr. Zalsman said.
Older people also seek help
A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.
The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.
“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.
Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.
SOURCE: Zalsman G. ECNP 2020, Session TP.06.
Suicidality appears to have increased sharply in Israel during the initial nationwide lockdown implemented in response to the COVID-19 pandemic, Gil Zalsman, MD, MHA, reported at the virtual congress of the European College of Neuropsychopharmacology.
He presented highlights from a soon-to-be-published analysis of the content of online chat sessions fielded by a national crisis hotline (Sahar.org.il) during the first 6 months of 2020, compared with January through June 2019, in the pre-COVID-19 era.
It’s far too early to say whether actual deaths tied to suicide rose significantly during the spring lockdown, since medical examiners often take a long time before ruling suicide as cause of death. But this much is clear: The number of suicide-related chat sessions recorded at the volunteer-staffed national hotline during April 2020 was two-and-a-half times greater than in April 2019, and threefold greater in May 2020 than a year earlier, according to Dr. Zalsman, professor of psychiatry at Tel Aviv University and director of the Geha Mental Health Center in Petach Tikva, Israel, where he also directs an adolescent day unit.
The proportion of chats handled at the crisis hotline, many of them concerned with the standard topics – relationships, stress, fears, anxiety, and other non–suicide-related issues – was 48% greater in the first half of 2020, compared with a year earlier. Indeed, the pandemic is putting an enormous strain on crisis hotlines the world over.
“Everybody who is working hotlines knows that they’re falling apart. There are too many calls, too many chats. They need to multiply their volunteers,” Dr. Zalsman said.
The number of suicide-related online chats jumped the week of March 12, when schools closed across Israel and a partial lockdown began. The peak in suicide-related chats occurred beginning the week of April 17, when the forced total lockdown was declared.
“Everything was closed. You couldn’t go out or the police would arrest you,” Dr. Zalsman recalled.
The suicide-related chat count started to drop off in mid-May, when schools reopened, and continued to decline through the end of June.
Only a small percentage of suicide-related chats were deemed by crisis hotline volunteers and their supervisors to be truly life-threatening situations necessitating a call to the police. But the number of such exchanges was significantly greater in April and May 2020 than in January and February, or in April and May 2019.
Use of the crisis hotline is ordinarily skewed toward tech-savvy young people, or as Dr. Zalsman called them, “kids who live inside their computers.” He note that the psychological impact of the pandemic on children and adolescents is largely unexplored research territory to date.
“ You can kill your grandfather by coughing,” Dr. Zalsman said.
Older people also seek help
A finding that he and his coinvestigators didn’t anticipate was the significantly increased use of the service by individuals aged 65 and older during the pandemic. This underscores the increased vulnerability of older people, which stems in part from their heightened risk for severe infection and consequent need for prolonged physical isolation, he said.
The conventional thinking among suicidologists is that during times of crisis – wars, natural disasters – suicidality plunges, then rises quickly afterward.
“People withhold themselves. When there’s a big danger from outside they ignore the danger from inside. And once the danger from outside is gone, they’re left with emptiness, unemployment, economic crisis, and they start” taking their own lives, Dr. Zalsman explained. He expects suicidality to increase after the pandemic, or as the Israeli crisis hotline data suggest, perhaps even during it, for multiple reasons. Patients with preexisting psychiatric disorders are often going untreated. The prolonged physical isolation causes emotional difficulties for some people, especially when accompanied by social isolation and loneliness. There is grief over the loss of friends and relatives because of COVID-19. And there is an expectation of looming economic hardship, with mounting unemployment and bankruptcies.
Dr. Zalsman reported having no financial conflicts regarding his study, conducted free of commercial support.
SOURCE: Zalsman G. ECNP 2020, Session TP.06.
FROM ECNP 2020
COVID-19 airway management: Expert tips on infection control
As continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.
This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”
During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”
In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”
When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”
He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.
Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.
Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”
Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).
To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”
For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.
For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO2 production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO2 production, and oxygen saturation, and adjust your vent settings as indicated.”
For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.
For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.
Dr. Griffis reported having no financial disclosures.
“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.
“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.
In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO2 requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.
I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”
As continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.
This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”
During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”
In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”
When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”
He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.
Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.
Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”
Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).
To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”
For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.
For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO2 production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO2 production, and oxygen saturation, and adjust your vent settings as indicated.”
For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.
For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.
Dr. Griffis reported having no financial disclosures.
“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.
“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.
In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO2 requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.
I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”
As continue to evolve, practicing vigilant transmission-based infection control precautions remains essential.
This starts with observing droplet precautions to prevent exposure to droplets larger than 5 microns in size, Charles Griffis, PhD, CRNA, said at a Society for Critical Care Medicine virtual meeting: COVID-19: What’s Next. “These are particles exhaled from infected persons and which fall within around 6 feet and involve an exposure time of 15 or more minutes of contact,” said Dr. Griffis, of the department of anesthesiology at the University of Southern California, Los Angeles. “We will always observe standard precautions, which include hand hygiene, gloves, hair and eye cover, medical mask, and face shield. We will observe these at all times for all patients and layer our transmission-based precautions on top.”
During aerosol-producing procedures such as airway management maneuvers, tracheostomies, and bronchoscopies, very fine microscopic particles less than 5 microns in size are produced, which remain airborne for potentially many hours and travel long distances. “We will add an N95 mask or a powered air-purifying respirator (PAPR) device to filter out tiny particles in addition to our ever-present standard precautions,” he said. “Contact precautions are indicated for direct contact with patient saliva, blood, urine, and stool. In addition to standard precautions, we’re going to add an impermeable gown and we’ll continue with gloves, eye protection, and shoe covers. The message is to all of us. We have to observe all of the infection precautions that all of us have learned and trained in to avoid exposure.”
In terms of airway management for infected patients for elective procedures and surgery, recommendations based on current and previous coronavirus outbreaks suggest that all patients get polymerase chain reaction (PCR) tested within 24-48 hours of elective procedures or surgeries. If positive, they should be quarantined for 10-14 days and then, if asymptomatic, these patients may be retested or they can be regarded as negative. “Patients who are PCR positive with active infection and active symptoms receive only urgent or emergent care in most settings,” said Dr. Griffis, a member of the American Association of Nurse Anesthetists Infection Control Advisory Panel. “The care provided to our patients, whether they’re positive or not, is individualized per patient needs and institutional policy. Some folks have made the decision to treat all patients as infected and to use airborne precautions for all aerosol-producing procedures for all patients all the time.”
When a COVID-19 patient requires emergent or urgent airway management because of respiratory failure or some other surgical or procedural intervention necessitating airway management, preprocedural planning is key, he continued. This means establishing the steps in airway management scenarios for infected patients and rehearsing those steps in each ICU setting with key personnel such as nurses, respiratory therapists, and medical staff. “You want to make sure that the PPE is readily available and determine and limit the number of personnel that are going to enter the patient’s room or area for airway management,” Dr. Griffis said. “Have all the airway equipment and drugs immediately available. Perhaps you could organize them in a cart which is decontaminated after every use.”
He also recommends forming an intubation team for ICUs and perhaps even for ORs, where the most experienced clinicians perform airway management. “This helps to avoid unnecessary airway manipulation and minimizes personnel exposure and time to airway establishment,” he said.
Always attempt to house the infected patient in an airborne isolation, negative-pressure room, with a minimum of 12 exchanges per hour and which will take 35 minutes for 99.99% removal of airborne contaminants after airway management. “These numbers are important to remember for room turnover safety,” he said.
Patient factors to review during airway management include assessing the past medical history, inspecting the airway and considering the patient’s current physiological status as time permits. Previously in the pandemic, intubation was used earlier in the disease course, but now data suggest that patients do better without intubation if possible (Am J Trop Med Hyg. 2020;102[6]. doi: 10.4269/aitmh.20-0283). “This is because the pathophysiology of COVID-19 is such that the lung tissue is predisposed to iatrogenic barotrauma damage from positive-pressure ventilation,” Dr. Griffis said. “In addition, COVID patients appear to tolerate significant hypoxemia without distress in many cases. Therefore, many clinicians now hold off on intubation until the hypoxemic patient begins exhibiting signs and symptoms of respiratory distress.”
Options for delivering noninvasive airway support for COVID-19 patients include high-flow nasal cannula and noninvasive positive-pressure ventilation via CPAP or BiPAP. To mitigate the associated aerosol production, consider applying a surgical mask, helmet, or face mask over the airway device/patient’s face. “Another measure that has proven helpful in general respiratory support is to actually put the patient in a prone position to help redistribute ventilation throughout the lungs,” Dr. Griffis said (see Resp Care. 2015;60[11]:1660-87).
To prepare for the actual intubation procedure, gather two expert intubators who are going to be entering the patient’s room. The team should perform hand hygiene and don full PPE prior to entry. “It’s recommended that you consider wearing double gloves for the intubation,” he said. “Have the airway equipment easily accessible in a central location on a cart or in a kit, and use disposable, single-use equipment if possible. All of the usual intubation equipment to maintain a clear airway and give positive pressure ventilation should be arranged for easy access. A video laryngoscope should be used, if possible, for greater accuracy and reduced procedure time. Ready access to sedation and muscle relaxant drugs must be assured at all times.”
For the intubation procedure itself, Dr. Griffis recommends ensuring that an oxygen source, positive-pressure ventilation, and suction and resuscitation drugs and equipment are available per institutional protocol. Assign one person outside the room to coordinate supplies and assistance. “Preoxygenate the patient as permitted by clinical status,” he said. “A nonrebreathing oxygen mask can be used if sufficient spontaneous ventilation is present. Assess the airway, check and arrange equipment for easy access, and develop the safest airway management plan. Consider a rapid sequence induction and intubation as the first option.” Avoid positive-pressure ventilation or awake fiber optic intubation unless absolutely necessary, thus avoiding aerosol production. “Only ventilate the patient after the endotracheal tube cuff is inflated, to avoid aerosol release,” he said.
For intubation, administer airway procedural drugs and insert the laryngoscope – ideally a video laryngoscope if available. Intubate the trachea under direct vision, inflate the cuff, and remove outer gloves. Then attach the Ambu bag with a 99% filtration efficiency, heat-and-moisture exchange filter; and proceed to ventilate the patient, checking for chest rise, breath sounds, and CO2 production. “Discard contaminated equipment in designated bins and secure the tube,” Dr. Griffis advised. “Attach the ventilator with an HMEF filter to protect the ventilator circuit and inner parts of the machine. Recheck your breath sounds, CO2 production, and oxygen saturation, and adjust your vent settings as indicated.”
For post intubation, Dr. Griffis recommends securing contaminated discardable equipment in biohazard-labeled bins or bags, safely doffing your PPE, and retaining your N95 mask in the room. Remove your inner gloves, perform hand hygiene with soap and water if available, with alcohol-based hand rub if not, then don clean gloves. Exit the room, safely transporting any contaminated equipment that will be reused such as a cart or video laryngoscope to decontamination areas for processing. “Once clear of the room, order your chest x-ray to confirm your tube position per institutional protocol, understanding that radiology techs are all going to be following infection control procedures and wearing their PPE,” he said.
For extubation, Dr. Griffis recommends excusing all nonessential personnel from the patient room and assigning an assistant outside the room for necessary help. An experienced airway management expert should evaluate the patient wearing full PPE and be double-gloved. “If the extubation criteria are met, suction the pharynx and extubate,” he said. “Remove outer gloves and apply desired oxygen delivery equipment to the patient and assess respiratory status and vital signs for stability.” Next, discard all contaminated equipment in designated bins, doff contaminated PPE, and retain your N95 mask. Doff inner gloves, perform hand hygiene, and don clean gloves. “Exit the room, hand off contaminated equipment that is reusable, doff your gloves outside, do hand hygiene, then proceed to change your scrubs and complete your own personal hygiene measures,” he said.
Dr. Griffis reported having no financial disclosures.
“While the PPE used for intubation of a coronavirus patient is certainly more than the typical droplet precautions observed when intubating any other patient, the process and best practices aren’t terribly different from usual standard of care: Ensuring all necessary equipment is readily available with backup plans should the airway be difficult,” said Megan Conroy, MD, assistant professor of clinical medicine at The Ohio State University.
“We’ve been streamlining the team that’s present in the room for intubations of COVID patients, but I’m always amazed at the team members that stand at the ready to lend additional assistance just from the other side of the door. So while fewer personnel may be exposed, I wouldn’t consider the team needed for intubation to actually be much smaller, we’re just functioning differently.
In my practice the decision of when to intubate, clinically, doesn’t vary too much from any other form of severe ARDS. We may tolerate higher FiO2 requirements on heated high-flow nasal cannula if the patient exhibits acceptable work of breathing, but I wouldn’t advise allowing a patient to remain hypoxemic with oxygen needs unmet by noninvasive methods out of fear of intubation or ventilator management. In my opinion, this simply delays a necessary therapy and only makes for a higher risk intubation. Certainly, the decision to intubate is never based on only one single data point, but takes an expert assessment of the whole clinical picture.
I’d assert that it’s true in every disease that patients do better if it’s possible to avoid intubation – but I would argue that the ability to avoid intubation is determined primarily by the disease course and clinical scenario, and not by whether the physician wishes to avoid intubation or not. If I can safely manage a patient off of a ventilator, I will always do so, COVID or otherwise. I think in this phase of the pandemic, patients ‘do better without intubation’ because those who didn’t require intubation were inherently doing better!”
FROM AN SCCM VIRTUAL MEETING
J&J’s one-shot COVID-19 vaccine advances to phase 3 testing
The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.
This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)
As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.
The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.
New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.
J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.
J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
Trials and tribulations
One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.
AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.
On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.
“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.
The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.
The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
Details of J&J trial
The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.
Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.
This article first appeared on Medscape.com.
The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.
This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)
As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.
The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.
New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.
J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.
J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
Trials and tribulations
One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.
AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.
On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.
“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.
The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.
The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
Details of J&J trial
The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.
Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.
This article first appeared on Medscape.com.
The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.
This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)
As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.
The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.
New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.
J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.
J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
Trials and tribulations
One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.
AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.
On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.
“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.
The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.
The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
Details of J&J trial
The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.
Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.
This article first appeared on Medscape.com.
CDC playbook prepares states for rollout of COVID-19 vaccine if one is approved
States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.
The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.
“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”
However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.
“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”
Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.
States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.
“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”
Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
Key issues identified
From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.
Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.
“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”
During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
A version of this article originally appeared on Medscape.com.
States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.
The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.
“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”
However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.
“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”
Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.
States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.
“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”
Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
Key issues identified
From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.
Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.
“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”
During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
A version of this article originally appeared on Medscape.com.
States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.
The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.
“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”
However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.
“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”
Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.
States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.
“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”
Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
Key issues identified
From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.
Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.
“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”
During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
A version of this article originally appeared on Medscape.com.
Three major COVID vaccine developers release detailed trial protocols
Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.
On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.
The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.
“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
AstraZeneca takes a shot at transparency
The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.
The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.
“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.
“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
Moderna methodology
The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.
A statement that was requested from ModernaTX was not received by press time.
Pfizer protocol
In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.
Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.
“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.
“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.
If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.
Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
A positive move
“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.
“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.
Kruse has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.
On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.
The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.
“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
AstraZeneca takes a shot at transparency
The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.
The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.
“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.
“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
Moderna methodology
The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.
A statement that was requested from ModernaTX was not received by press time.
Pfizer protocol
In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.
Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.
“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.
“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.
If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.
Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
A positive move
“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.
“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.
Kruse has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.
On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.
The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.
“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
AstraZeneca takes a shot at transparency
The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.
The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.
“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.
“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
Moderna methodology
The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.
A statement that was requested from ModernaTX was not received by press time.
Pfizer protocol
In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.
Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.
“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.
“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.
If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.
Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
A positive move
“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.
“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.
Kruse has disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Children’s share of COVID-19 burden continues to increase
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
Signs of an ‘October vaccine surprise’ alarm career scientists
who have pledged not to release any vaccine unless it’s proved safe and effective.
In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.
It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.
If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.
The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.
Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.
“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”
Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.
Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.
After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.
“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.
White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.
Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”
Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.
Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.
Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.
The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”
Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.
Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.
Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.
AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.
Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.
“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”
In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”
But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.
Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.
Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.
A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.
“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.
Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”
In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.
But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.
Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
who have pledged not to release any vaccine unless it’s proved safe and effective.
In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.
It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.
If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.
The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.
Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.
“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”
Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.
Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.
After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.
“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.
White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.
Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”
Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.
Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.
Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.
The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”
Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.
Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.
Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.
AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.
Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.
“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”
In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”
But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.
Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.
Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.
A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.
“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.
Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”
In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.
But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.
Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
who have pledged not to release any vaccine unless it’s proved safe and effective.
In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.
It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.
If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.
The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.
Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.
“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”
Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.
Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.
After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.
“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.
White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.
Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”
Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.
Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.
Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.
The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”
Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.
Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.
Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.
AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.
Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.
“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”
In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”
But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.
Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.
Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.
A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.
“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.
Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”
In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.
But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.
Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”
Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.
COVID-19 Screening and Testing Among Patients With Neurologic Dysfunction: The Neuro-COVID-19 Time-out Process and Checklist
From the University of Mississippi Medical Center, Department of Neurology, Division of Neuroscience Intensive Care, Jackson, MS.
Abstract
Objective: To test a coronavirus disease 2019 (COVID-19) screening tool to identify patients who qualify for testing among patients with neurologic dysfunction who are unable to answer the usual screening questions, which could help to prevent unprotected exposure of patients and health care workers to COVID-19.
Methods: The Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) was implemented at our institution for 1 week as a quality improvement project to improve the pathway for COVID-19 screening and testing among patients with neurologic dysfunction.
Results: A total of 14 new patients were admitted into the neuroscience intensive care unit (NSICU) service during the pilot period. The NCOT-PC was utilized on 9 (64%) patients with neurologic dysfunction; 7 of these patients were found to have a likelihood of requiring testing based on the NCOT-PC and were subsequently screened for COVID-19 testing by contacting the institution’s COVID-19 testing hotline (Med-Com). All these patients were subsequently transitioned into person-under-investigation status based on the determination from Med-Com. The NSICU staff involved were able to utilize NCOT-PC without issues. The NCOT-PC was immediately adopted into the NSICU process.
Conclusion: Use of the NCOT-PC tool was found to be feasible and improved the screening methodology of patients with neurologic dysfunction.
Keywords: coronavirus; health care planning; quality improvement; patient safety; medical decision-making; neuroscience intensive care unit.
The coronavirus disease 2019 (COVID-19) pandemic has altered various standard emergent care pathways. Current recommendations regarding COVID-19 screening for testing involve asking patients about their symptoms, including fever, cough, chest pain, and dyspnea.1 This standard screening method poses a problem when caring for patients with neurologic dysfunction. COVID-19 patients may pre-sent with conditions that affect their ability to answer questions, such as stroke, encephalitis, neuromuscular disorders, or headache, and that may preclude the use of standard screening for testing.2 Patients with acute neurologic dysfunction who cannot undergo standard screening may leave the emergency department (ED) and transition into the neuroscience intensive care unit (NSICU) or any intensive care unit (ICU) without a reliable COVID-19 screening test.
The Protected Code Stroke pathway offers protection in the emergent setting for patients with stroke when their COVID-19 status is unknown.3 A similar process has been applied at our institution for emergent management of patients with cerebrovascular disease (stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). However, the process from the ED after designating “difficult to screen” patients as persons under investigation (PUI) is unclear. The Centers for Disease Control and Prevention (CDC) has delineated the priorities for testing, with not all declared PUIs requiring testing.4 This poses a great challenge, because patients designated as PUIs require the same management as a COVID-19-positive patient, with negative-pressure isolation rooms as well as use of protective personal equipment (PPE), which may not be readily available. It was also recognized that, because the ED staff can be overwhelmed by COVID-19 patients, there may not be enough time to perform detailed screening of patients with neurologic dysfunction and that “reverse masking” may not be done consistently for nonintubated patients. This may place patients and health care workers at risk of unprotected exposure.
Recognizing these challenges, we created a Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) as a quality improvement project. The aim of this project was to improve and standardize the current process of identifying patients with neurologic dysfunction who require COVID-19 testing to decrease the risk of unprotected exposure of patients and health care workers.
Methods
Patients and Definitions
This quality improvement project was undertaken at the University of Mississippi Medical Center NSICU. Because this was a quality improvement project, an Institutional Review Board exemption was granted.
The NCOT-PC was utilized in consecutive patients with neurologic dysfunction admitted to the NSICU during a period of 1 week. “Neurologic dysfunction” encompasses any neurologic illness affecting the mental status and/or level of alertness, subsequently precluding the ability to reliably screen the patient utilizing standard COVID-19 screening. “Med-Com” at our institution is the equivalent of the national COVID-19 testing hotline, where our institution’s infectious diseases experts screen calls for testing and determine whether testing is warranted. “Unprotected exposure” means exposure to COVID-19 without adequate and appropriate PPE.
Quality Improvement Process
As more PUIs were being admitted to the institution, we used the Plan-Do-Study-Act method for process improvements in the NSICU.5 NSICU stakeholders, including attendings, the nurse manager, and nurse practitioners (NPs), developed an algorithm to facilitate the coordination of the NSICU staff in screening patients to identify those with a high likelihood of needing COVID-19 testing upon arrival in the NSICU (Figure 1). Once the NCOT-PC was finalized, NSICU stakeholders were educated regarding the use of this screening tool.
The checklist clinicians review when screening patients is shown in Figure 2. The risk factors comprising the checklist include patient history and clinical and radiographic characteristics that have been shown to be relevant for identifying patients with COVID-19.6,7 The imaging criteria utilize imaging that is part of the standard of care for NSICU patients. For example, computed tomography angiogram of the head and neck performed as part of the acute stroke protocol captures the upper part of the chest. These images are utilized for their incidental findings, such as apical ground-glass opacities and tree-in-bud formation. The risk factors applicable to the patient determine whether the clinician will call Med-Com for testing approval. Institutional COVID-19 processes were then followed accordingly.8 The decision from Med-Com was considered final, and no deviation from institutional policies was allowed.
NCOT-PC was utilized for consecutive days for 1 week before re-evaluation of its feasibility and adaptability.
Data Collection and Analysis
Consecutive patients with neurologic dysfunction admitted into the NSICU were assigned nonlinkable patient numbers. No identifiers were collected for the purpose of this project. The primary diagnosis for admission, the neurologic dysfunction that precluded standard screening, and checklist components that the patient fulfilled were collected.
To assess the tool’s feasibility, feedback regarding the ease of use of the NCOT-PC was gathered from the nurses, NPs, charge nurses, fellows, and other attendings. To assess the utility of the NCOT-PC in identifying patients who will be approved for COVID-19 testing, we calculated the proportion of patients who were deemed to have a high likelihood of testing and the proportion of patients who were approved for testing. Descriptive statistics were used, as applicable for the project, to summarize the utility of the NCOT-PC.
Results
We found that the NCOT-PC can be easily used by clinicians. The NSICU staff did not communicate any implementation issues, and since the NCOT-PC was implemented, no problems have been identified.
During the pilot period of the NCOT-PC, 14 new patients were admitted to the NSICU service. Nine (64%) of these had neurologic dysfunction, and the NCOT-PC was used to determine whether Med-Com should be called based on the patients’ likelihood (high vs low) of needing a COVID-19 test. Of those patients with neurologic dysfunction, 7 (78%) were deemed to have a high likelihood of needing a COVID-19 test based on the NCOT-PC. Med-Com was contacted regarding these patients, and all were deemed to require the COVID-19 test by Med-Com and were transitioned into PUI status per institutional policy (Table).
Discussion
The NCOT-PC project improved and standardized the process of identifying and screening patients with neurologic dysfunction for COVID-19 testing. The screening tool is feasible to use, and it decreased inadvertent unprotected exposure of patients and health care workers.
The NCOT-PC was easy to administer. Educating the staff regarding the new process took only a few minutes and involved a meeting with the nurse manager, NPs, fellows, residents, and attendings. We found that this process works well in tandem with the standard institutional processes in place in terms of Protected Code Stroke pathway, PUI isolation, PPE use, and Med-Com screening for COVID-19 testing. Med-Com was called only if the patient fulfilled the checklist criteria. In addition, no extra cost was attributed to implementing the NCOT-PC, since we utilized imaging that was already done as part of the standard of care for patients with neurologic dysfunction.
The standardization of the process of screening for COVID-19 testing among patients with neurologic dysfunction improved patient selection. Before the NCOT-PC, there was no consistency in terms of who should get tested and the reason for testing patients with neurologic dysfunction. Patients can pass through the ED and arrive in the NSICU with an unclear screening status, which may cause inadvertent patient and health care worker exposure to COVID-19. With the NCOT-PC, we have avoided instances of inadvertent staff or patient exposure in the NSICU.
The NCOT-PC was adopted into the NSICU process after the first week it was piloted. Beyond the NSICU, the application of the NCOT-PC can be extended to any patient presentation that precludes standard screening, such as ED and interhospital transfers for stroke codes, trauma codes, code blue, or myocardial infarction codes. In our department, as we started the process of PCS for stroke codes, we included NCOT-PC for stroke patients with neurologic dysfunction.
The results of our initiative are largely limited by the decision-making process of Med-Com when patients are called in for testing. At the time of our project, there were no specific criteria used for patients with altered mental status, except for the standard screening methods, and it was through clinician-to-clinician discussion that testing decisions were made. Another limitation is the short period of time that the NCOT-PC was applied before adoption.
In summary, the NCOT-PC tool improved the screening process for COVID-19 testing in patients with neurologic dysfunction admitted to the NSICU. It was feasible and prevented unprotected staff and patient exposure to COVID-19. The NCOT-PC functionality was compatible with institutional COVID-19 policies in place, which contributed to its overall sustainability.
The Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) were utilized in preparing this manuscript.9
Acknowledgment: The authors thank the University of Mississippi Medical Center NSICU staff for their input with implementation of the NCOT-PC.
Corresponding author: Prashant A. Natteru, MD, University of Mississippi Medical Center, Department of Neurology, 2500 North State St., Jackson, MS 39216; pnatteru@umc.edu.
Financial disclosures: None.
1. Coronavirus disease 2019 (COVID-19) Symptoms. www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed April 9, 2020.
2. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:1-9.
3. Khosravani H, Rajendram P, Notario L, et al. Protected code stroke: hyperacute stroke management during the coronavirus disease 2019. (COVID-19) pandemic. Stroke. 2020;51:1891-1895.
4. Coronavirus disease 2019 (COVID-19) evaluation and testing. www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html. Accessed April 9, 2020.
5. Plan-Do-Study-Act Worksheet. Institute for Healthcare Improvement website. www.ihi.org/resources/Pages/Tools/PlanDoStudyActWorksheet.aspx. Accessed March 31,2020.
6. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;10.1002/jmv.25728.
7. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;101623.
8. UMMC’s COVID-19 Clinical Processes. www.umc.edu/CoronaVirus/Mississippi-Health-Care-Professionals/Clinical-Resources/Clinical-Resources.html. Accessed April 9, 2020.
9. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): Revised Publication Guidelines from a Detailed Consensus Process. The EQUATOR Network. www.equator-network.org/reporting-guidelines/squire/. Accessed May 12, 2020.
From the University of Mississippi Medical Center, Department of Neurology, Division of Neuroscience Intensive Care, Jackson, MS.
Abstract
Objective: To test a coronavirus disease 2019 (COVID-19) screening tool to identify patients who qualify for testing among patients with neurologic dysfunction who are unable to answer the usual screening questions, which could help to prevent unprotected exposure of patients and health care workers to COVID-19.
Methods: The Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) was implemented at our institution for 1 week as a quality improvement project to improve the pathway for COVID-19 screening and testing among patients with neurologic dysfunction.
Results: A total of 14 new patients were admitted into the neuroscience intensive care unit (NSICU) service during the pilot period. The NCOT-PC was utilized on 9 (64%) patients with neurologic dysfunction; 7 of these patients were found to have a likelihood of requiring testing based on the NCOT-PC and were subsequently screened for COVID-19 testing by contacting the institution’s COVID-19 testing hotline (Med-Com). All these patients were subsequently transitioned into person-under-investigation status based on the determination from Med-Com. The NSICU staff involved were able to utilize NCOT-PC without issues. The NCOT-PC was immediately adopted into the NSICU process.
Conclusion: Use of the NCOT-PC tool was found to be feasible and improved the screening methodology of patients with neurologic dysfunction.
Keywords: coronavirus; health care planning; quality improvement; patient safety; medical decision-making; neuroscience intensive care unit.
The coronavirus disease 2019 (COVID-19) pandemic has altered various standard emergent care pathways. Current recommendations regarding COVID-19 screening for testing involve asking patients about their symptoms, including fever, cough, chest pain, and dyspnea.1 This standard screening method poses a problem when caring for patients with neurologic dysfunction. COVID-19 patients may pre-sent with conditions that affect their ability to answer questions, such as stroke, encephalitis, neuromuscular disorders, or headache, and that may preclude the use of standard screening for testing.2 Patients with acute neurologic dysfunction who cannot undergo standard screening may leave the emergency department (ED) and transition into the neuroscience intensive care unit (NSICU) or any intensive care unit (ICU) without a reliable COVID-19 screening test.
The Protected Code Stroke pathway offers protection in the emergent setting for patients with stroke when their COVID-19 status is unknown.3 A similar process has been applied at our institution for emergent management of patients with cerebrovascular disease (stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). However, the process from the ED after designating “difficult to screen” patients as persons under investigation (PUI) is unclear. The Centers for Disease Control and Prevention (CDC) has delineated the priorities for testing, with not all declared PUIs requiring testing.4 This poses a great challenge, because patients designated as PUIs require the same management as a COVID-19-positive patient, with negative-pressure isolation rooms as well as use of protective personal equipment (PPE), which may not be readily available. It was also recognized that, because the ED staff can be overwhelmed by COVID-19 patients, there may not be enough time to perform detailed screening of patients with neurologic dysfunction and that “reverse masking” may not be done consistently for nonintubated patients. This may place patients and health care workers at risk of unprotected exposure.
Recognizing these challenges, we created a Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) as a quality improvement project. The aim of this project was to improve and standardize the current process of identifying patients with neurologic dysfunction who require COVID-19 testing to decrease the risk of unprotected exposure of patients and health care workers.
Methods
Patients and Definitions
This quality improvement project was undertaken at the University of Mississippi Medical Center NSICU. Because this was a quality improvement project, an Institutional Review Board exemption was granted.
The NCOT-PC was utilized in consecutive patients with neurologic dysfunction admitted to the NSICU during a period of 1 week. “Neurologic dysfunction” encompasses any neurologic illness affecting the mental status and/or level of alertness, subsequently precluding the ability to reliably screen the patient utilizing standard COVID-19 screening. “Med-Com” at our institution is the equivalent of the national COVID-19 testing hotline, where our institution’s infectious diseases experts screen calls for testing and determine whether testing is warranted. “Unprotected exposure” means exposure to COVID-19 without adequate and appropriate PPE.
Quality Improvement Process
As more PUIs were being admitted to the institution, we used the Plan-Do-Study-Act method for process improvements in the NSICU.5 NSICU stakeholders, including attendings, the nurse manager, and nurse practitioners (NPs), developed an algorithm to facilitate the coordination of the NSICU staff in screening patients to identify those with a high likelihood of needing COVID-19 testing upon arrival in the NSICU (Figure 1). Once the NCOT-PC was finalized, NSICU stakeholders were educated regarding the use of this screening tool.
The checklist clinicians review when screening patients is shown in Figure 2. The risk factors comprising the checklist include patient history and clinical and radiographic characteristics that have been shown to be relevant for identifying patients with COVID-19.6,7 The imaging criteria utilize imaging that is part of the standard of care for NSICU patients. For example, computed tomography angiogram of the head and neck performed as part of the acute stroke protocol captures the upper part of the chest. These images are utilized for their incidental findings, such as apical ground-glass opacities and tree-in-bud formation. The risk factors applicable to the patient determine whether the clinician will call Med-Com for testing approval. Institutional COVID-19 processes were then followed accordingly.8 The decision from Med-Com was considered final, and no deviation from institutional policies was allowed.
NCOT-PC was utilized for consecutive days for 1 week before re-evaluation of its feasibility and adaptability.
Data Collection and Analysis
Consecutive patients with neurologic dysfunction admitted into the NSICU were assigned nonlinkable patient numbers. No identifiers were collected for the purpose of this project. The primary diagnosis for admission, the neurologic dysfunction that precluded standard screening, and checklist components that the patient fulfilled were collected.
To assess the tool’s feasibility, feedback regarding the ease of use of the NCOT-PC was gathered from the nurses, NPs, charge nurses, fellows, and other attendings. To assess the utility of the NCOT-PC in identifying patients who will be approved for COVID-19 testing, we calculated the proportion of patients who were deemed to have a high likelihood of testing and the proportion of patients who were approved for testing. Descriptive statistics were used, as applicable for the project, to summarize the utility of the NCOT-PC.
Results
We found that the NCOT-PC can be easily used by clinicians. The NSICU staff did not communicate any implementation issues, and since the NCOT-PC was implemented, no problems have been identified.
During the pilot period of the NCOT-PC, 14 new patients were admitted to the NSICU service. Nine (64%) of these had neurologic dysfunction, and the NCOT-PC was used to determine whether Med-Com should be called based on the patients’ likelihood (high vs low) of needing a COVID-19 test. Of those patients with neurologic dysfunction, 7 (78%) were deemed to have a high likelihood of needing a COVID-19 test based on the NCOT-PC. Med-Com was contacted regarding these patients, and all were deemed to require the COVID-19 test by Med-Com and were transitioned into PUI status per institutional policy (Table).
Discussion
The NCOT-PC project improved and standardized the process of identifying and screening patients with neurologic dysfunction for COVID-19 testing. The screening tool is feasible to use, and it decreased inadvertent unprotected exposure of patients and health care workers.
The NCOT-PC was easy to administer. Educating the staff regarding the new process took only a few minutes and involved a meeting with the nurse manager, NPs, fellows, residents, and attendings. We found that this process works well in tandem with the standard institutional processes in place in terms of Protected Code Stroke pathway, PUI isolation, PPE use, and Med-Com screening for COVID-19 testing. Med-Com was called only if the patient fulfilled the checklist criteria. In addition, no extra cost was attributed to implementing the NCOT-PC, since we utilized imaging that was already done as part of the standard of care for patients with neurologic dysfunction.
The standardization of the process of screening for COVID-19 testing among patients with neurologic dysfunction improved patient selection. Before the NCOT-PC, there was no consistency in terms of who should get tested and the reason for testing patients with neurologic dysfunction. Patients can pass through the ED and arrive in the NSICU with an unclear screening status, which may cause inadvertent patient and health care worker exposure to COVID-19. With the NCOT-PC, we have avoided instances of inadvertent staff or patient exposure in the NSICU.
The NCOT-PC was adopted into the NSICU process after the first week it was piloted. Beyond the NSICU, the application of the NCOT-PC can be extended to any patient presentation that precludes standard screening, such as ED and interhospital transfers for stroke codes, trauma codes, code blue, or myocardial infarction codes. In our department, as we started the process of PCS for stroke codes, we included NCOT-PC for stroke patients with neurologic dysfunction.
The results of our initiative are largely limited by the decision-making process of Med-Com when patients are called in for testing. At the time of our project, there were no specific criteria used for patients with altered mental status, except for the standard screening methods, and it was through clinician-to-clinician discussion that testing decisions were made. Another limitation is the short period of time that the NCOT-PC was applied before adoption.
In summary, the NCOT-PC tool improved the screening process for COVID-19 testing in patients with neurologic dysfunction admitted to the NSICU. It was feasible and prevented unprotected staff and patient exposure to COVID-19. The NCOT-PC functionality was compatible with institutional COVID-19 policies in place, which contributed to its overall sustainability.
The Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) were utilized in preparing this manuscript.9
Acknowledgment: The authors thank the University of Mississippi Medical Center NSICU staff for their input with implementation of the NCOT-PC.
Corresponding author: Prashant A. Natteru, MD, University of Mississippi Medical Center, Department of Neurology, 2500 North State St., Jackson, MS 39216; pnatteru@umc.edu.
Financial disclosures: None.
From the University of Mississippi Medical Center, Department of Neurology, Division of Neuroscience Intensive Care, Jackson, MS.
Abstract
Objective: To test a coronavirus disease 2019 (COVID-19) screening tool to identify patients who qualify for testing among patients with neurologic dysfunction who are unable to answer the usual screening questions, which could help to prevent unprotected exposure of patients and health care workers to COVID-19.
Methods: The Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) was implemented at our institution for 1 week as a quality improvement project to improve the pathway for COVID-19 screening and testing among patients with neurologic dysfunction.
Results: A total of 14 new patients were admitted into the neuroscience intensive care unit (NSICU) service during the pilot period. The NCOT-PC was utilized on 9 (64%) patients with neurologic dysfunction; 7 of these patients were found to have a likelihood of requiring testing based on the NCOT-PC and were subsequently screened for COVID-19 testing by contacting the institution’s COVID-19 testing hotline (Med-Com). All these patients were subsequently transitioned into person-under-investigation status based on the determination from Med-Com. The NSICU staff involved were able to utilize NCOT-PC without issues. The NCOT-PC was immediately adopted into the NSICU process.
Conclusion: Use of the NCOT-PC tool was found to be feasible and improved the screening methodology of patients with neurologic dysfunction.
Keywords: coronavirus; health care planning; quality improvement; patient safety; medical decision-making; neuroscience intensive care unit.
The coronavirus disease 2019 (COVID-19) pandemic has altered various standard emergent care pathways. Current recommendations regarding COVID-19 screening for testing involve asking patients about their symptoms, including fever, cough, chest pain, and dyspnea.1 This standard screening method poses a problem when caring for patients with neurologic dysfunction. COVID-19 patients may pre-sent with conditions that affect their ability to answer questions, such as stroke, encephalitis, neuromuscular disorders, or headache, and that may preclude the use of standard screening for testing.2 Patients with acute neurologic dysfunction who cannot undergo standard screening may leave the emergency department (ED) and transition into the neuroscience intensive care unit (NSICU) or any intensive care unit (ICU) without a reliable COVID-19 screening test.
The Protected Code Stroke pathway offers protection in the emergent setting for patients with stroke when their COVID-19 status is unknown.3 A similar process has been applied at our institution for emergent management of patients with cerebrovascular disease (stroke, intracerebral hemorrhage, and subarachnoid hemorrhage). However, the process from the ED after designating “difficult to screen” patients as persons under investigation (PUI) is unclear. The Centers for Disease Control and Prevention (CDC) has delineated the priorities for testing, with not all declared PUIs requiring testing.4 This poses a great challenge, because patients designated as PUIs require the same management as a COVID-19-positive patient, with negative-pressure isolation rooms as well as use of protective personal equipment (PPE), which may not be readily available. It was also recognized that, because the ED staff can be overwhelmed by COVID-19 patients, there may not be enough time to perform detailed screening of patients with neurologic dysfunction and that “reverse masking” may not be done consistently for nonintubated patients. This may place patients and health care workers at risk of unprotected exposure.
Recognizing these challenges, we created a Neuro-COVID-19 Time-out Process and Checklist (NCOT-PC) as a quality improvement project. The aim of this project was to improve and standardize the current process of identifying patients with neurologic dysfunction who require COVID-19 testing to decrease the risk of unprotected exposure of patients and health care workers.
Methods
Patients and Definitions
This quality improvement project was undertaken at the University of Mississippi Medical Center NSICU. Because this was a quality improvement project, an Institutional Review Board exemption was granted.
The NCOT-PC was utilized in consecutive patients with neurologic dysfunction admitted to the NSICU during a period of 1 week. “Neurologic dysfunction” encompasses any neurologic illness affecting the mental status and/or level of alertness, subsequently precluding the ability to reliably screen the patient utilizing standard COVID-19 screening. “Med-Com” at our institution is the equivalent of the national COVID-19 testing hotline, where our institution’s infectious diseases experts screen calls for testing and determine whether testing is warranted. “Unprotected exposure” means exposure to COVID-19 without adequate and appropriate PPE.
Quality Improvement Process
As more PUIs were being admitted to the institution, we used the Plan-Do-Study-Act method for process improvements in the NSICU.5 NSICU stakeholders, including attendings, the nurse manager, and nurse practitioners (NPs), developed an algorithm to facilitate the coordination of the NSICU staff in screening patients to identify those with a high likelihood of needing COVID-19 testing upon arrival in the NSICU (Figure 1). Once the NCOT-PC was finalized, NSICU stakeholders were educated regarding the use of this screening tool.
The checklist clinicians review when screening patients is shown in Figure 2. The risk factors comprising the checklist include patient history and clinical and radiographic characteristics that have been shown to be relevant for identifying patients with COVID-19.6,7 The imaging criteria utilize imaging that is part of the standard of care for NSICU patients. For example, computed tomography angiogram of the head and neck performed as part of the acute stroke protocol captures the upper part of the chest. These images are utilized for their incidental findings, such as apical ground-glass opacities and tree-in-bud formation. The risk factors applicable to the patient determine whether the clinician will call Med-Com for testing approval. Institutional COVID-19 processes were then followed accordingly.8 The decision from Med-Com was considered final, and no deviation from institutional policies was allowed.
NCOT-PC was utilized for consecutive days for 1 week before re-evaluation of its feasibility and adaptability.
Data Collection and Analysis
Consecutive patients with neurologic dysfunction admitted into the NSICU were assigned nonlinkable patient numbers. No identifiers were collected for the purpose of this project. The primary diagnosis for admission, the neurologic dysfunction that precluded standard screening, and checklist components that the patient fulfilled were collected.
To assess the tool’s feasibility, feedback regarding the ease of use of the NCOT-PC was gathered from the nurses, NPs, charge nurses, fellows, and other attendings. To assess the utility of the NCOT-PC in identifying patients who will be approved for COVID-19 testing, we calculated the proportion of patients who were deemed to have a high likelihood of testing and the proportion of patients who were approved for testing. Descriptive statistics were used, as applicable for the project, to summarize the utility of the NCOT-PC.
Results
We found that the NCOT-PC can be easily used by clinicians. The NSICU staff did not communicate any implementation issues, and since the NCOT-PC was implemented, no problems have been identified.
During the pilot period of the NCOT-PC, 14 new patients were admitted to the NSICU service. Nine (64%) of these had neurologic dysfunction, and the NCOT-PC was used to determine whether Med-Com should be called based on the patients’ likelihood (high vs low) of needing a COVID-19 test. Of those patients with neurologic dysfunction, 7 (78%) were deemed to have a high likelihood of needing a COVID-19 test based on the NCOT-PC. Med-Com was contacted regarding these patients, and all were deemed to require the COVID-19 test by Med-Com and were transitioned into PUI status per institutional policy (Table).
Discussion
The NCOT-PC project improved and standardized the process of identifying and screening patients with neurologic dysfunction for COVID-19 testing. The screening tool is feasible to use, and it decreased inadvertent unprotected exposure of patients and health care workers.
The NCOT-PC was easy to administer. Educating the staff regarding the new process took only a few minutes and involved a meeting with the nurse manager, NPs, fellows, residents, and attendings. We found that this process works well in tandem with the standard institutional processes in place in terms of Protected Code Stroke pathway, PUI isolation, PPE use, and Med-Com screening for COVID-19 testing. Med-Com was called only if the patient fulfilled the checklist criteria. In addition, no extra cost was attributed to implementing the NCOT-PC, since we utilized imaging that was already done as part of the standard of care for patients with neurologic dysfunction.
The standardization of the process of screening for COVID-19 testing among patients with neurologic dysfunction improved patient selection. Before the NCOT-PC, there was no consistency in terms of who should get tested and the reason for testing patients with neurologic dysfunction. Patients can pass through the ED and arrive in the NSICU with an unclear screening status, which may cause inadvertent patient and health care worker exposure to COVID-19. With the NCOT-PC, we have avoided instances of inadvertent staff or patient exposure in the NSICU.
The NCOT-PC was adopted into the NSICU process after the first week it was piloted. Beyond the NSICU, the application of the NCOT-PC can be extended to any patient presentation that precludes standard screening, such as ED and interhospital transfers for stroke codes, trauma codes, code blue, or myocardial infarction codes. In our department, as we started the process of PCS for stroke codes, we included NCOT-PC for stroke patients with neurologic dysfunction.
The results of our initiative are largely limited by the decision-making process of Med-Com when patients are called in for testing. At the time of our project, there were no specific criteria used for patients with altered mental status, except for the standard screening methods, and it was through clinician-to-clinician discussion that testing decisions were made. Another limitation is the short period of time that the NCOT-PC was applied before adoption.
In summary, the NCOT-PC tool improved the screening process for COVID-19 testing in patients with neurologic dysfunction admitted to the NSICU. It was feasible and prevented unprotected staff and patient exposure to COVID-19. The NCOT-PC functionality was compatible with institutional COVID-19 policies in place, which contributed to its overall sustainability.
The Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) were utilized in preparing this manuscript.9
Acknowledgment: The authors thank the University of Mississippi Medical Center NSICU staff for their input with implementation of the NCOT-PC.
Corresponding author: Prashant A. Natteru, MD, University of Mississippi Medical Center, Department of Neurology, 2500 North State St., Jackson, MS 39216; pnatteru@umc.edu.
Financial disclosures: None.
1. Coronavirus disease 2019 (COVID-19) Symptoms. www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed April 9, 2020.
2. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:1-9.
3. Khosravani H, Rajendram P, Notario L, et al. Protected code stroke: hyperacute stroke management during the coronavirus disease 2019. (COVID-19) pandemic. Stroke. 2020;51:1891-1895.
4. Coronavirus disease 2019 (COVID-19) evaluation and testing. www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html. Accessed April 9, 2020.
5. Plan-Do-Study-Act Worksheet. Institute for Healthcare Improvement website. www.ihi.org/resources/Pages/Tools/PlanDoStudyActWorksheet.aspx. Accessed March 31,2020.
6. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;10.1002/jmv.25728.
7. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;101623.
8. UMMC’s COVID-19 Clinical Processes. www.umc.edu/CoronaVirus/Mississippi-Health-Care-Professionals/Clinical-Resources/Clinical-Resources.html. Accessed April 9, 2020.
9. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): Revised Publication Guidelines from a Detailed Consensus Process. The EQUATOR Network. www.equator-network.org/reporting-guidelines/squire/. Accessed May 12, 2020.
1. Coronavirus disease 2019 (COVID-19) Symptoms. www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html. Accessed April 9, 2020.
2. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020;77:1-9.
3. Khosravani H, Rajendram P, Notario L, et al. Protected code stroke: hyperacute stroke management during the coronavirus disease 2019. (COVID-19) pandemic. Stroke. 2020;51:1891-1895.
4. Coronavirus disease 2019 (COVID-19) evaluation and testing. www.cdc.gov/coronavirus/2019-nCoV/hcp/clinical-criteria.html. Accessed April 9, 2020.
5. Plan-Do-Study-Act Worksheet. Institute for Healthcare Improvement website. www.ihi.org/resources/Pages/Tools/PlanDoStudyActWorksheet.aspx. Accessed March 31,2020.
6. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;10.1002/jmv.25728.
7. Rodriguez-Morales AJ, Cardona-Ospina JA, Gutiérrez-Ocampo E, et al. Clinical, laboratory and imaging features of COVID-19: A systematic review and meta-analysis. Travel Med Infect Dis. 2020;101623.
8. UMMC’s COVID-19 Clinical Processes. www.umc.edu/CoronaVirus/Mississippi-Health-Care-Professionals/Clinical-Resources/Clinical-Resources.html. Accessed April 9, 2020.
9. SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence): Revised Publication Guidelines from a Detailed Consensus Process. The EQUATOR Network. www.equator-network.org/reporting-guidelines/squire/. Accessed May 12, 2020.
“I Really Didn’t Want To Come In”: The Unseen Effects of COVID-19 on Children
The Children’s Hospital of Philadelphia, Philadelphia, PA.
The effects of COVID-19 on children’s health are multifaceted. In comparison to adults, children typically experience far milder physical consequences when infected with the virus. A notable exception is the newly described multisystem inflammatory syndrome associated with COVID-19 (MIS-C), which has proven to be a source of significant morbidity among the children it affects.1 Nevertheless, even those children not infected with COVID-19 have suffered due to the disease. School closures have deprived children of opportunities for social and academic growth and, in some cases, the provision of food, social services, medication administration, and many different therapies. Social distancing rules have limited play among children, which is crucial to their development and mental health. The impact on children who have lost family members, including parents, is monumental. Amidst all of this observable suffering, however, the pandemic poses a less visible threat to the health of children.
It is well documented that concern about exposure to COVID-19 has led many adults to avoid emergency departments (EDs) around the world. We believe parents may be avoiding ED visits for their children for the same reason. In the United States, ED volumes dropped approximately 50% during spring 2020.2 While EDs saw increasing, and at times overwhelming, numbers of patients with COVID-19, the number of patients presenting with other life-threatening medical issues, including heart attacks and strokes, declined.3,4 Data from the National Center for Health Statistics this past spring revealed nationwide increases in deaths due to nonrespiratory causes such as diabetes, heart disease, and stroke.5 ED avoidance and unprecedented lack of access to outpatient care, though with the intent to reduce overall risk, are likely significant contributors to these deaths.
Pediatric patients, especially the most vulnerable, are similarly at risk for deleterious health-related consequences from ED avoidance and from limited access to primary and outpatient specialty care. Data from Europe indicate dramatic drops in pediatric ED (PED) volumes, as well as an increase in the proportion of ED visits leading to hospitalization.6,7 These studies suggest that when patients do ultimately present to the PED, they may be more seriously ill.
At our institution, we have seen many COVID-19-negative patients whose medical care has been negatively influenced by the pandemic. A few months ago, a 1-month-old infant with an underlying health condition presented to the PED in extremis after weeks of progressively worsening feeding issues. The infant had been closely followed by the primary care provider (PCP) and subspecialty team via phone calls, televisits, and some office visits. Both physicians and parents had tried to resolve the feeding issues within the outpatient context, explicitly hoping to avoid potential exposure of this fragile patient to COVID-19 in the hospital. On eventual presentation to the PED, the infant was profoundly dehydrated, with significant electrolyte derangement and an acute abdomen, requiring admission to the intensive care unit. Ultimately, a new diagnosis of Hirschsprung disease was made, and the infant was hospitalized for several weeks for weight gain.
Later this summer, a school-aged child with a history of poorly controlled type 1 diabetes presented to an affiliated community hospital comatose and with Kussmaul respirations. Prior to the pandemic, a school nurse administered the child’s morning insulin. Since school closed, the patient had been responsible for administering this dose of insulin while the parents worked outside the home. Despite close and frequent communication between the patient’s endocrinology team and the family, the patient’s glucose and ketone levels began to rise. The parent administered repeated boluses of insulin at home in an attempt to avoid the perceived exposure risk associated with an ED visit. On presentation to the PED, the patient was profoundly altered, with a pH of 7.0. When transfer to a tertiary care center was recommended, the patient’s parent expressed persistent concerns about COVID-19 exposure in the larger hospital, although ultimately consent to transfer was given.
A third case from this summer provides an example of a different type of patient affected by COVID-19: the neonate whose birth circumstances were altered due to the virus. A 3-day-old, full-term infant presented to the ED with hypothermia after PCP referral. The parents had considered both home birth and hospital delivery earlier in the pregnancy, ultimately opting for home birth due to concerns about COVID-19 exposure in the hospital. The pregnancy and delivery were uncomplicated. The neonate did not receive the first hepatitis B vaccine, erythromycin eye ointment, or vitamin K after delivery. In the first 3 days of life, the patient had voided once and stooled once per day. The patient’s mother, inexperienced with breastfeeding and without access to a lactation consultant, was unsure about latch or emptying of her breasts. At the first pediatrician visit, the infant was noted to be hypothermic to 35°C, intermittently bradycardic to the 80s, and with diminished arousal. In the PED, a full sepsis work-up was initiated. Though multiple attempts were made by different providers, only a minimal amount of blood could be drawn, presumably due to dehydration. Of note, the neonate received vitamin K subcutaneously prior to lumbar puncture.
Pediatricians across the country have gone to great lengths to protect their patients and to provide high-quality care both inside and outside the office during this unprecedented time. Nevertheless, these 3 cases illustrate the detrimental effects of COVID-19 on the delivery of pediatric health care. The first 2 cases in particular demonstrate the limitations of even close and consistent phone and televisit follow-up. Telehealth has provided a lifeline for patients and families during the pandemic, and, in most cases, has provided an excellent temporary substitution for office visits. There are, however, limitations to care without physical evaluation. Had the children in the first 2 cases been evaluated in person sooner, they may have been referred to a higher level of care more expediently. Likewise, in all 3 cases, parental reservations about exposing their children to COVID-19 through a trip to the hospital, however well-intentioned, likely played a role in the eventual severity of illness with which each child presented to the hospital.
If we are encountering children in the PED with severe illness due to delayed presentation to care, what about the children we aren’t seeing? As COVID-19 cases rise daily in the United States, we must be aware of the possibility of ED avoidance. We propose a multimodal approach to combat this dangerous phenomenon. Inpatient and ED-based pediatricians must maintain clear and open lines of communication with outpatient colleagues so that we can partner in considering which cases warrant prompt ED evaluation, even in the midst of a pandemic. All pediatricians must remind families that our hospitals remain open and ready to treat children safely. We must promote community awareness of the numerous safety precautions we take every day so that patients and families can feel comfortable seeking care at the hospital; the message of ED and hospital safety must be even more robust for caregivers of our particularly vulnerable children. As always, how we communicate with patients and their families matters. Validating and addressing concerns about COVID-19 exposure, while providing reassurance about the safety of our hospitals, could save children’s lives.
Acknowledgment: Thank you to Dr. Cynthia Mollen and Dr. Kathy Shaw for their reviews of the manuscript.
Corresponding author: Regina L. Toto, MD, Department of Pediatrics, The Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104; totor@email.chop.edu.
Financial disclosures: None.
Keywords: coronavirus; pediatric; children; access to care; emergency department.
1. Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607-1608.
2. Wong LE, Hawkins JE, Langness S, et al. Where are all the patients? addressing COVID-19 fear to encourage sick patients to seek emergency care. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0193
3. Moroni F, Gramegna M, Ajello S, et al. Collateral damage: medical care avoidance behavior among patients with acute coronary syndrome during the COVID-19 pandemic. JACC. 2020. doi:10.1016/j.jaccas.2020.04.010
4. Deerberg-Wittram J, Knothe C. Do not stay home: we are ready for you. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0146
5. Woolf SH, Chapman DA, Sabo RT, et al. Excess deaths From COVID-19 and other causes, March-April 2020. JAMA. 2020. doi:10.1001.jama.2020.11787
6. Lazzerini M, Barbi E, Apicella A, et al. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health. 2020;4:E10-1.
7. Happle C, Dopfer C, Wetzke M, et al. Covid-19 related reduction in paediatric emergency healthcare utilization--a concerning trend. BMC Pediatrics. [under review]. 2020. doi:10.21203/rs.3.rs-2
The Children’s Hospital of Philadelphia, Philadelphia, PA.
The effects of COVID-19 on children’s health are multifaceted. In comparison to adults, children typically experience far milder physical consequences when infected with the virus. A notable exception is the newly described multisystem inflammatory syndrome associated with COVID-19 (MIS-C), which has proven to be a source of significant morbidity among the children it affects.1 Nevertheless, even those children not infected with COVID-19 have suffered due to the disease. School closures have deprived children of opportunities for social and academic growth and, in some cases, the provision of food, social services, medication administration, and many different therapies. Social distancing rules have limited play among children, which is crucial to their development and mental health. The impact on children who have lost family members, including parents, is monumental. Amidst all of this observable suffering, however, the pandemic poses a less visible threat to the health of children.
It is well documented that concern about exposure to COVID-19 has led many adults to avoid emergency departments (EDs) around the world. We believe parents may be avoiding ED visits for their children for the same reason. In the United States, ED volumes dropped approximately 50% during spring 2020.2 While EDs saw increasing, and at times overwhelming, numbers of patients with COVID-19, the number of patients presenting with other life-threatening medical issues, including heart attacks and strokes, declined.3,4 Data from the National Center for Health Statistics this past spring revealed nationwide increases in deaths due to nonrespiratory causes such as diabetes, heart disease, and stroke.5 ED avoidance and unprecedented lack of access to outpatient care, though with the intent to reduce overall risk, are likely significant contributors to these deaths.
Pediatric patients, especially the most vulnerable, are similarly at risk for deleterious health-related consequences from ED avoidance and from limited access to primary and outpatient specialty care. Data from Europe indicate dramatic drops in pediatric ED (PED) volumes, as well as an increase in the proportion of ED visits leading to hospitalization.6,7 These studies suggest that when patients do ultimately present to the PED, they may be more seriously ill.
At our institution, we have seen many COVID-19-negative patients whose medical care has been negatively influenced by the pandemic. A few months ago, a 1-month-old infant with an underlying health condition presented to the PED in extremis after weeks of progressively worsening feeding issues. The infant had been closely followed by the primary care provider (PCP) and subspecialty team via phone calls, televisits, and some office visits. Both physicians and parents had tried to resolve the feeding issues within the outpatient context, explicitly hoping to avoid potential exposure of this fragile patient to COVID-19 in the hospital. On eventual presentation to the PED, the infant was profoundly dehydrated, with significant electrolyte derangement and an acute abdomen, requiring admission to the intensive care unit. Ultimately, a new diagnosis of Hirschsprung disease was made, and the infant was hospitalized for several weeks for weight gain.
Later this summer, a school-aged child with a history of poorly controlled type 1 diabetes presented to an affiliated community hospital comatose and with Kussmaul respirations. Prior to the pandemic, a school nurse administered the child’s morning insulin. Since school closed, the patient had been responsible for administering this dose of insulin while the parents worked outside the home. Despite close and frequent communication between the patient’s endocrinology team and the family, the patient’s glucose and ketone levels began to rise. The parent administered repeated boluses of insulin at home in an attempt to avoid the perceived exposure risk associated with an ED visit. On presentation to the PED, the patient was profoundly altered, with a pH of 7.0. When transfer to a tertiary care center was recommended, the patient’s parent expressed persistent concerns about COVID-19 exposure in the larger hospital, although ultimately consent to transfer was given.
A third case from this summer provides an example of a different type of patient affected by COVID-19: the neonate whose birth circumstances were altered due to the virus. A 3-day-old, full-term infant presented to the ED with hypothermia after PCP referral. The parents had considered both home birth and hospital delivery earlier in the pregnancy, ultimately opting for home birth due to concerns about COVID-19 exposure in the hospital. The pregnancy and delivery were uncomplicated. The neonate did not receive the first hepatitis B vaccine, erythromycin eye ointment, or vitamin K after delivery. In the first 3 days of life, the patient had voided once and stooled once per day. The patient’s mother, inexperienced with breastfeeding and without access to a lactation consultant, was unsure about latch or emptying of her breasts. At the first pediatrician visit, the infant was noted to be hypothermic to 35°C, intermittently bradycardic to the 80s, and with diminished arousal. In the PED, a full sepsis work-up was initiated. Though multiple attempts were made by different providers, only a minimal amount of blood could be drawn, presumably due to dehydration. Of note, the neonate received vitamin K subcutaneously prior to lumbar puncture.
Pediatricians across the country have gone to great lengths to protect their patients and to provide high-quality care both inside and outside the office during this unprecedented time. Nevertheless, these 3 cases illustrate the detrimental effects of COVID-19 on the delivery of pediatric health care. The first 2 cases in particular demonstrate the limitations of even close and consistent phone and televisit follow-up. Telehealth has provided a lifeline for patients and families during the pandemic, and, in most cases, has provided an excellent temporary substitution for office visits. There are, however, limitations to care without physical evaluation. Had the children in the first 2 cases been evaluated in person sooner, they may have been referred to a higher level of care more expediently. Likewise, in all 3 cases, parental reservations about exposing their children to COVID-19 through a trip to the hospital, however well-intentioned, likely played a role in the eventual severity of illness with which each child presented to the hospital.
If we are encountering children in the PED with severe illness due to delayed presentation to care, what about the children we aren’t seeing? As COVID-19 cases rise daily in the United States, we must be aware of the possibility of ED avoidance. We propose a multimodal approach to combat this dangerous phenomenon. Inpatient and ED-based pediatricians must maintain clear and open lines of communication with outpatient colleagues so that we can partner in considering which cases warrant prompt ED evaluation, even in the midst of a pandemic. All pediatricians must remind families that our hospitals remain open and ready to treat children safely. We must promote community awareness of the numerous safety precautions we take every day so that patients and families can feel comfortable seeking care at the hospital; the message of ED and hospital safety must be even more robust for caregivers of our particularly vulnerable children. As always, how we communicate with patients and their families matters. Validating and addressing concerns about COVID-19 exposure, while providing reassurance about the safety of our hospitals, could save children’s lives.
Acknowledgment: Thank you to Dr. Cynthia Mollen and Dr. Kathy Shaw for their reviews of the manuscript.
Corresponding author: Regina L. Toto, MD, Department of Pediatrics, The Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104; totor@email.chop.edu.
Financial disclosures: None.
Keywords: coronavirus; pediatric; children; access to care; emergency department.
The Children’s Hospital of Philadelphia, Philadelphia, PA.
The effects of COVID-19 on children’s health are multifaceted. In comparison to adults, children typically experience far milder physical consequences when infected with the virus. A notable exception is the newly described multisystem inflammatory syndrome associated with COVID-19 (MIS-C), which has proven to be a source of significant morbidity among the children it affects.1 Nevertheless, even those children not infected with COVID-19 have suffered due to the disease. School closures have deprived children of opportunities for social and academic growth and, in some cases, the provision of food, social services, medication administration, and many different therapies. Social distancing rules have limited play among children, which is crucial to their development and mental health. The impact on children who have lost family members, including parents, is monumental. Amidst all of this observable suffering, however, the pandemic poses a less visible threat to the health of children.
It is well documented that concern about exposure to COVID-19 has led many adults to avoid emergency departments (EDs) around the world. We believe parents may be avoiding ED visits for their children for the same reason. In the United States, ED volumes dropped approximately 50% during spring 2020.2 While EDs saw increasing, and at times overwhelming, numbers of patients with COVID-19, the number of patients presenting with other life-threatening medical issues, including heart attacks and strokes, declined.3,4 Data from the National Center for Health Statistics this past spring revealed nationwide increases in deaths due to nonrespiratory causes such as diabetes, heart disease, and stroke.5 ED avoidance and unprecedented lack of access to outpatient care, though with the intent to reduce overall risk, are likely significant contributors to these deaths.
Pediatric patients, especially the most vulnerable, are similarly at risk for deleterious health-related consequences from ED avoidance and from limited access to primary and outpatient specialty care. Data from Europe indicate dramatic drops in pediatric ED (PED) volumes, as well as an increase in the proportion of ED visits leading to hospitalization.6,7 These studies suggest that when patients do ultimately present to the PED, they may be more seriously ill.
At our institution, we have seen many COVID-19-negative patients whose medical care has been negatively influenced by the pandemic. A few months ago, a 1-month-old infant with an underlying health condition presented to the PED in extremis after weeks of progressively worsening feeding issues. The infant had been closely followed by the primary care provider (PCP) and subspecialty team via phone calls, televisits, and some office visits. Both physicians and parents had tried to resolve the feeding issues within the outpatient context, explicitly hoping to avoid potential exposure of this fragile patient to COVID-19 in the hospital. On eventual presentation to the PED, the infant was profoundly dehydrated, with significant electrolyte derangement and an acute abdomen, requiring admission to the intensive care unit. Ultimately, a new diagnosis of Hirschsprung disease was made, and the infant was hospitalized for several weeks for weight gain.
Later this summer, a school-aged child with a history of poorly controlled type 1 diabetes presented to an affiliated community hospital comatose and with Kussmaul respirations. Prior to the pandemic, a school nurse administered the child’s morning insulin. Since school closed, the patient had been responsible for administering this dose of insulin while the parents worked outside the home. Despite close and frequent communication between the patient’s endocrinology team and the family, the patient’s glucose and ketone levels began to rise. The parent administered repeated boluses of insulin at home in an attempt to avoid the perceived exposure risk associated with an ED visit. On presentation to the PED, the patient was profoundly altered, with a pH of 7.0. When transfer to a tertiary care center was recommended, the patient’s parent expressed persistent concerns about COVID-19 exposure in the larger hospital, although ultimately consent to transfer was given.
A third case from this summer provides an example of a different type of patient affected by COVID-19: the neonate whose birth circumstances were altered due to the virus. A 3-day-old, full-term infant presented to the ED with hypothermia after PCP referral. The parents had considered both home birth and hospital delivery earlier in the pregnancy, ultimately opting for home birth due to concerns about COVID-19 exposure in the hospital. The pregnancy and delivery were uncomplicated. The neonate did not receive the first hepatitis B vaccine, erythromycin eye ointment, or vitamin K after delivery. In the first 3 days of life, the patient had voided once and stooled once per day. The patient’s mother, inexperienced with breastfeeding and without access to a lactation consultant, was unsure about latch or emptying of her breasts. At the first pediatrician visit, the infant was noted to be hypothermic to 35°C, intermittently bradycardic to the 80s, and with diminished arousal. In the PED, a full sepsis work-up was initiated. Though multiple attempts were made by different providers, only a minimal amount of blood could be drawn, presumably due to dehydration. Of note, the neonate received vitamin K subcutaneously prior to lumbar puncture.
Pediatricians across the country have gone to great lengths to protect their patients and to provide high-quality care both inside and outside the office during this unprecedented time. Nevertheless, these 3 cases illustrate the detrimental effects of COVID-19 on the delivery of pediatric health care. The first 2 cases in particular demonstrate the limitations of even close and consistent phone and televisit follow-up. Telehealth has provided a lifeline for patients and families during the pandemic, and, in most cases, has provided an excellent temporary substitution for office visits. There are, however, limitations to care without physical evaluation. Had the children in the first 2 cases been evaluated in person sooner, they may have been referred to a higher level of care more expediently. Likewise, in all 3 cases, parental reservations about exposing their children to COVID-19 through a trip to the hospital, however well-intentioned, likely played a role in the eventual severity of illness with which each child presented to the hospital.
If we are encountering children in the PED with severe illness due to delayed presentation to care, what about the children we aren’t seeing? As COVID-19 cases rise daily in the United States, we must be aware of the possibility of ED avoidance. We propose a multimodal approach to combat this dangerous phenomenon. Inpatient and ED-based pediatricians must maintain clear and open lines of communication with outpatient colleagues so that we can partner in considering which cases warrant prompt ED evaluation, even in the midst of a pandemic. All pediatricians must remind families that our hospitals remain open and ready to treat children safely. We must promote community awareness of the numerous safety precautions we take every day so that patients and families can feel comfortable seeking care at the hospital; the message of ED and hospital safety must be even more robust for caregivers of our particularly vulnerable children. As always, how we communicate with patients and their families matters. Validating and addressing concerns about COVID-19 exposure, while providing reassurance about the safety of our hospitals, could save children’s lives.
Acknowledgment: Thank you to Dr. Cynthia Mollen and Dr. Kathy Shaw for their reviews of the manuscript.
Corresponding author: Regina L. Toto, MD, Department of Pediatrics, The Children’s Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA 19104; totor@email.chop.edu.
Financial disclosures: None.
Keywords: coronavirus; pediatric; children; access to care; emergency department.
1. Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607-1608.
2. Wong LE, Hawkins JE, Langness S, et al. Where are all the patients? addressing COVID-19 fear to encourage sick patients to seek emergency care. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0193
3. Moroni F, Gramegna M, Ajello S, et al. Collateral damage: medical care avoidance behavior among patients with acute coronary syndrome during the COVID-19 pandemic. JACC. 2020. doi:10.1016/j.jaccas.2020.04.010
4. Deerberg-Wittram J, Knothe C. Do not stay home: we are ready for you. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0146
5. Woolf SH, Chapman DA, Sabo RT, et al. Excess deaths From COVID-19 and other causes, March-April 2020. JAMA. 2020. doi:10.1001.jama.2020.11787
6. Lazzerini M, Barbi E, Apicella A, et al. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health. 2020;4:E10-1.
7. Happle C, Dopfer C, Wetzke M, et al. Covid-19 related reduction in paediatric emergency healthcare utilization--a concerning trend. BMC Pediatrics. [under review]. 2020. doi:10.21203/rs.3.rs-2
1. Riphagen S, Gomez X, Gonzalez-Martinez C, et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395:1607-1608.
2. Wong LE, Hawkins JE, Langness S, et al. Where are all the patients? addressing COVID-19 fear to encourage sick patients to seek emergency care. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0193
3. Moroni F, Gramegna M, Ajello S, et al. Collateral damage: medical care avoidance behavior among patients with acute coronary syndrome during the COVID-19 pandemic. JACC. 2020. doi:10.1016/j.jaccas.2020.04.010
4. Deerberg-Wittram J, Knothe C. Do not stay home: we are ready for you. NEJM Catalyst. 2020. doi:10.1056/CAT.20.0146
5. Woolf SH, Chapman DA, Sabo RT, et al. Excess deaths From COVID-19 and other causes, March-April 2020. JAMA. 2020. doi:10.1001.jama.2020.11787
6. Lazzerini M, Barbi E, Apicella A, et al. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health. 2020;4:E10-1.
7. Happle C, Dopfer C, Wetzke M, et al. Covid-19 related reduction in paediatric emergency healthcare utilization--a concerning trend. BMC Pediatrics. [under review]. 2020. doi:10.21203/rs.3.rs-2
Systemic Corticosteroids in Critically Ill Patients With COVID-19
Study Overview
Objective. To assess the association between administration of systemic corticosteroids, compared with usual care or placebo, and 28-day all-cause mortality in critically ill patients with coronavirus disease 2019 (COVID-19).
Design. Prospective meta-analysis with data from 7 randomized clinical trials conducted in 12 countries.
Setting and participants. This prospective meta-analysis included randomized clinical trials conducted between February 26, 2020, and June 9, 2020, that examined the clinical efficacy of administration of corticosteroids in hospitalized COVID-19 patients who were critically ill. Trials were systematically identified from ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the EU Clinical Trials Register, using the search terms COVID-19, corticosteroids, and steroids. Additional trials were identified by experts from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Senior investigators of these identified trials were asked to participate in weekly calls to develop a protocol for the prospective meta-analysis.1 Subsequently, trials that had randomly assigned critically ill patients to receive corticosteroids versus usual care or placebo were invited to participate in this meta-analysis. Data were pooled from patients recruited to the participating trials through June 9, 2020, and aggregated in overall and in predefined subgroups.
Main outcome measures. The primary outcome was all-cause mortality up to 30 days after randomization. Because 5 of the included trials reported mortality at 28 days after randomization, the primary outcome was reported as 28-day all-cause mortality. The secondary outcome was serious adverse events (SAEs). The authors also gathered data on the demographic and clinical characteristics of patients, the number of patients lost to follow-up, and outcomes according to intervention group, overall, and in subgroups (ie, patients receiving invasive mechanical ventilation or vasoactive medication; age ≤ 60 years or > 60 years [the median across trials]; sex [male or female]; and the duration patients were symptomatic [≤ 7 days or > 7 days]). For each trial, the risk of bias was assessed independently by 4 investigators using the Cochrane Risk of Bias Assessment Tool for the overall effects of corticosteroids on mortality and SAEs and the effect of assignment and allocated interventions. Inconsistency between trial results was evaluated using the I2 statistic. The trials were classified according to the corticosteroids used in the intervention group and the dose administered using a priori-defined cutoffs (15 mg/day of dexamethasone, 400 mg/day of hydrocortisone, and 1 mg/kg/day of methylprednisolone). The primary analysis utilized was an inverse variance-weighted fixed-effect meta-analysis of odds ratios (ORs) for overall mortality. Random-effects meta-analyses with Paule-Mandel estimate of heterogeneity were also performed.
Main results. Seven trials (DEXA-COVID 19, CoDEX, RECOVERY, CAPE COVID, COVID STEROID, REMAP-CAP, and Steroids-SARI) were included in the final meta-analysis. The enrolled patients were from Australia, Brazil, Canada, China, Denmark, France, Ireland, the Netherlands, New Zealand, Spain, the United Kingdom, and the United States. The date of final follow-up was July 6, 2020. The corticosteroids groups included dexamethasone at low (6 mg/day orally or intravenously [IV]) and high (20 mg/day IV) doses; low-dose hydrocortisone (200 mg/day IV or 50 mg every 6 hr IV); and high-dose methylprednisolone (40 mg every 12 hr IV). In total, 1703 patients were randomized, with 678 assigned to the corticosteroids group and 1025 to the usual-care or placebo group. The median age of patients was 60 years (interquartile range, 52-68 years), and 29% were women. The larger number of patients in the usual-care/placebo group was a result of the 1:2 randomization (corticosteroids versus usual care or placebo) in the RECOVERY trial, which contributed 59.1% of patients included in this prospective meta-analysis. The majority of patients were receiving invasive mechanical ventilation at randomization (1559 patients). The administration of adjunctive treatments, such as azithromycin or antiviral agents, varied among the trials. The risk of bias was determined as low for 6 of the 7 mortality results.
A total of 222 of 678 patients in the corticosteroids group died, and 425 of 1025 patients in the usual care or placebo group died. The summary OR was 0.66 (95% confidence interval [CI], 0.53-0.82; P < 0.001) based on a fixed-effect meta-analysis, and 0.70 (95% CI, 0.48-1.01; P = 0.053) based on the random-effects meta-analysis, for 28-day all-cause mortality comparing all corticosteroids with usual care or placebo. There was little inconsistency between trial results (I2 = 15.6%; P = 0.31). The fixed-effect summary OR for the association with 28-day all-cause mortality was 0.64 (95% CI, 0.50-0.82; P < 0.001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths); the OR was 0.69 (95% CI, 0.43-1.12; P = 0.13) for hydrocortisone (3 trials, 374 patients, and 94 deaths); and the OR was 0.91 (95% CI, 0.29-2.87; P = 0.87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Moreover, in trials that administered low-dose corticosteroids, the overall fixed-effect OR for 28-day all-cause mortality was 0.61 (95% CI, 0.48-0.78; P < 0.001). In the subgroup analysis, the overall fixed-effect OR was 0.69 (95% CI, 0.55-0.86) in patients who were receiving invasive mechanical ventilation at randomization, and the OR was 0.41 (95% CI, 0.19-0.88) in patients who were not receiving invasive mechanical ventilation at randomization.
Six trials (all except the RECOVERY trial) reported SAEs, with 64 events occurring among 354 patients assigned to the corticosteroids group and 80 SAEs occurring among 342 patients assigned to the usual-care or placebo group. There was no suggestion that the risk of SAEs was higher in patients who were administered corticosteroids.
Conclusion. The administration of systemic corticosteroids was associated with a lower 28-day all-cause mortality in critically ill patients with COVID-19 compared to those who received usual care or placebo.
Commentary
Corticosteroids are anti-inflammatory and vasoconstrictive medications that have long been used in intensive care units for the treatment of acute respiratory distress syndrome and septic shock. However, the therapeutic role of corticosteroids for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was uncertain at the outset of the COVID-19 pandemic due to concerns that this class of medications may cause an impaired immune response in the setting of a life-threatening SARS-CoV-2 infection. Evidence supporting this notion included prior studies showing that corticosteroid therapy was associated with delayed viral clearance of Middle East respiratory syndrome or a higher viral load of SARS-CoV.2,3 The uncertainty surrounding the therapeutic use of corticosteroids in treating COVID-19 led to a simultaneous global effort to conduct randomized controlled trials to urgently examine this important clinical question. The open-label Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, conducted in the UK, was the first large-scale randomized clinical trial that reported the clinical benefit of corticosteroids in treating patients hospitalized with COVID-19. Specifically, it showed that low-dose dexamethasone (6 mg/day) administered orally or IV for up to 10 days resulted in a 2.8% absolute reduction in 28-day mortality, with the greatest benefit, an absolute risk reduction of 12.1%, conferred to patients who were receiving invasive mechanical ventilation at the time of randomization.4 In response to these findings, the National Institutes of Health COVID-19 Treatment Guidelines Panel recommended the use of dexamethasone in patients with COVID-19 who are on mechanical ventilation or who require supplemental oxygen, and recommended against the use of dexamethasone for those not requiring supplemental oxygen.5
The meta-analysis discussed in this commentary, conducted by the WHO REACT Working Group, has replicated initial findings from the RECOVERY trial. This prospective meta-analysis pooled data from 7 randomized controlled trials of corticosteroid therapy in 1703 critically ill patients hospitalized with COVID-19. Similar to findings from the RECOVERY trial, corticosteroids were associated with lower all-cause mortality at 28 days after randomization, and this benefit was observed both in critically ill patients who were receiving mechanical ventilation or supplemental oxygen without mechanical ventilation. Interestingly, while the OR estimates were imprecise, the reduction in mortality rates was similar between patients who were administered dexamethasone and hydrocortisone, which may suggest a general drug class effect. In addition, the mortality benefit of corticosteroids appeared similar for those aged ≤ 60 years and those aged > 60 years, between female and male patients, and those who were symptomatic for ≤ 7 days or > 7 days before randomization. Moreover, the administration of corticosteroids did not appear to increase the risk of SAEs. While more data are needed, results from the RECOVERY trial and this prospective meta-analysis indicate that corticosteroids should be an essential pharmacologic treatment for COVID-19, and suggest its potential role as a standard of care for critically ill patients with COVID-19.
This study has several limitations. First, not all trials systematically identified participated in the meta-analysis. Second, long-term outcomes after hospital discharge were not captured, and thus the effect of corticosteroids on long-term mortality and other adverse outcomes, such as hospital readmission, remain unknown. Third, because children were excluded from study participation, the effect of corticosteroids on pediatric COVID-19 patients is unknown. Fourth, the RECOVERY trial contributed more than 50% of patients in the current analysis, although there was little inconsistency in the effects of corticosteroids on mortality between individual trials. Last, the meta-analysis was unable to establish the optimal dose or duration of corticosteroid intervention in critically ill COVID-19 patients, or determine its efficacy in patients with mild-to-moderate COVID-19, all of which are key clinical questions that will need to be addressed with further clinical investigations.
The development of effective treatments for COVID-19 is critical to mitigating the devastating consequences of SARS-CoV-2 infection. Several recent COVID-19 clinical trials have shown promise in this endeavor. For instance, the Adaptive COVID-19 Treatment Trial (ACCT-1) found that intravenous remdesivir, as compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.6 Moreover, there is some evidence to suggest that convalescent plasma and aerosol inhalation of IFN-κ may have beneficial effects in treating COVID-19.7,8 Thus, clinical trials designed to investigate combination therapy approaches including corticosteroids, remdesivir, convalescent plasma, and others are urgently needed to help identify interventions that most effectively treat COVID-19.
Applications for Clinical Practice
The use of corticosteroids in critically ill patients with COVID-19 reduces overall mortality. This treatment is inexpensive and available in most care settings, including low-resource regions, and provides hope for better outcomes in the COVID-19 pandemic.
Katerina Oikonomou, MD, PhD
General Hospital of Larissa, Larissa, Greece
Fred Ko, MD, MS
1. Sterne JAC, Diaz J, Villar J, et al. Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials. Trials. 2020;21:734.
2. Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31:304-309.
3. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for citically Ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197:757-767.
4. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19 - preliminary report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020;NEJMoa2021436.
5. NIH COVID-19 Treatment Guidelines. National Institutes of Health. www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/. Accessed September 11, 2020.
6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19--preliminary report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;NEJMoa2007764.
7. Casadevall A, Joyner MJ, Pirofski LA. A randomized trial of convalescent plasma for covid-19-potentially hopeful signals. JAMA. 2020;324:455-457.
8. Fu W, Liu Y, Xia L, et al. A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19. EClinicalMedicine. 2020;25:100478.
Study Overview
Objective. To assess the association between administration of systemic corticosteroids, compared with usual care or placebo, and 28-day all-cause mortality in critically ill patients with coronavirus disease 2019 (COVID-19).
Design. Prospective meta-analysis with data from 7 randomized clinical trials conducted in 12 countries.
Setting and participants. This prospective meta-analysis included randomized clinical trials conducted between February 26, 2020, and June 9, 2020, that examined the clinical efficacy of administration of corticosteroids in hospitalized COVID-19 patients who were critically ill. Trials were systematically identified from ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the EU Clinical Trials Register, using the search terms COVID-19, corticosteroids, and steroids. Additional trials were identified by experts from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Senior investigators of these identified trials were asked to participate in weekly calls to develop a protocol for the prospective meta-analysis.1 Subsequently, trials that had randomly assigned critically ill patients to receive corticosteroids versus usual care or placebo were invited to participate in this meta-analysis. Data were pooled from patients recruited to the participating trials through June 9, 2020, and aggregated in overall and in predefined subgroups.
Main outcome measures. The primary outcome was all-cause mortality up to 30 days after randomization. Because 5 of the included trials reported mortality at 28 days after randomization, the primary outcome was reported as 28-day all-cause mortality. The secondary outcome was serious adverse events (SAEs). The authors also gathered data on the demographic and clinical characteristics of patients, the number of patients lost to follow-up, and outcomes according to intervention group, overall, and in subgroups (ie, patients receiving invasive mechanical ventilation or vasoactive medication; age ≤ 60 years or > 60 years [the median across trials]; sex [male or female]; and the duration patients were symptomatic [≤ 7 days or > 7 days]). For each trial, the risk of bias was assessed independently by 4 investigators using the Cochrane Risk of Bias Assessment Tool for the overall effects of corticosteroids on mortality and SAEs and the effect of assignment and allocated interventions. Inconsistency between trial results was evaluated using the I2 statistic. The trials were classified according to the corticosteroids used in the intervention group and the dose administered using a priori-defined cutoffs (15 mg/day of dexamethasone, 400 mg/day of hydrocortisone, and 1 mg/kg/day of methylprednisolone). The primary analysis utilized was an inverse variance-weighted fixed-effect meta-analysis of odds ratios (ORs) for overall mortality. Random-effects meta-analyses with Paule-Mandel estimate of heterogeneity were also performed.
Main results. Seven trials (DEXA-COVID 19, CoDEX, RECOVERY, CAPE COVID, COVID STEROID, REMAP-CAP, and Steroids-SARI) were included in the final meta-analysis. The enrolled patients were from Australia, Brazil, Canada, China, Denmark, France, Ireland, the Netherlands, New Zealand, Spain, the United Kingdom, and the United States. The date of final follow-up was July 6, 2020. The corticosteroids groups included dexamethasone at low (6 mg/day orally or intravenously [IV]) and high (20 mg/day IV) doses; low-dose hydrocortisone (200 mg/day IV or 50 mg every 6 hr IV); and high-dose methylprednisolone (40 mg every 12 hr IV). In total, 1703 patients were randomized, with 678 assigned to the corticosteroids group and 1025 to the usual-care or placebo group. The median age of patients was 60 years (interquartile range, 52-68 years), and 29% were women. The larger number of patients in the usual-care/placebo group was a result of the 1:2 randomization (corticosteroids versus usual care or placebo) in the RECOVERY trial, which contributed 59.1% of patients included in this prospective meta-analysis. The majority of patients were receiving invasive mechanical ventilation at randomization (1559 patients). The administration of adjunctive treatments, such as azithromycin or antiviral agents, varied among the trials. The risk of bias was determined as low for 6 of the 7 mortality results.
A total of 222 of 678 patients in the corticosteroids group died, and 425 of 1025 patients in the usual care or placebo group died. The summary OR was 0.66 (95% confidence interval [CI], 0.53-0.82; P < 0.001) based on a fixed-effect meta-analysis, and 0.70 (95% CI, 0.48-1.01; P = 0.053) based on the random-effects meta-analysis, for 28-day all-cause mortality comparing all corticosteroids with usual care or placebo. There was little inconsistency between trial results (I2 = 15.6%; P = 0.31). The fixed-effect summary OR for the association with 28-day all-cause mortality was 0.64 (95% CI, 0.50-0.82; P < 0.001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths); the OR was 0.69 (95% CI, 0.43-1.12; P = 0.13) for hydrocortisone (3 trials, 374 patients, and 94 deaths); and the OR was 0.91 (95% CI, 0.29-2.87; P = 0.87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Moreover, in trials that administered low-dose corticosteroids, the overall fixed-effect OR for 28-day all-cause mortality was 0.61 (95% CI, 0.48-0.78; P < 0.001). In the subgroup analysis, the overall fixed-effect OR was 0.69 (95% CI, 0.55-0.86) in patients who were receiving invasive mechanical ventilation at randomization, and the OR was 0.41 (95% CI, 0.19-0.88) in patients who were not receiving invasive mechanical ventilation at randomization.
Six trials (all except the RECOVERY trial) reported SAEs, with 64 events occurring among 354 patients assigned to the corticosteroids group and 80 SAEs occurring among 342 patients assigned to the usual-care or placebo group. There was no suggestion that the risk of SAEs was higher in patients who were administered corticosteroids.
Conclusion. The administration of systemic corticosteroids was associated with a lower 28-day all-cause mortality in critically ill patients with COVID-19 compared to those who received usual care or placebo.
Commentary
Corticosteroids are anti-inflammatory and vasoconstrictive medications that have long been used in intensive care units for the treatment of acute respiratory distress syndrome and septic shock. However, the therapeutic role of corticosteroids for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was uncertain at the outset of the COVID-19 pandemic due to concerns that this class of medications may cause an impaired immune response in the setting of a life-threatening SARS-CoV-2 infection. Evidence supporting this notion included prior studies showing that corticosteroid therapy was associated with delayed viral clearance of Middle East respiratory syndrome or a higher viral load of SARS-CoV.2,3 The uncertainty surrounding the therapeutic use of corticosteroids in treating COVID-19 led to a simultaneous global effort to conduct randomized controlled trials to urgently examine this important clinical question. The open-label Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, conducted in the UK, was the first large-scale randomized clinical trial that reported the clinical benefit of corticosteroids in treating patients hospitalized with COVID-19. Specifically, it showed that low-dose dexamethasone (6 mg/day) administered orally or IV for up to 10 days resulted in a 2.8% absolute reduction in 28-day mortality, with the greatest benefit, an absolute risk reduction of 12.1%, conferred to patients who were receiving invasive mechanical ventilation at the time of randomization.4 In response to these findings, the National Institutes of Health COVID-19 Treatment Guidelines Panel recommended the use of dexamethasone in patients with COVID-19 who are on mechanical ventilation or who require supplemental oxygen, and recommended against the use of dexamethasone for those not requiring supplemental oxygen.5
The meta-analysis discussed in this commentary, conducted by the WHO REACT Working Group, has replicated initial findings from the RECOVERY trial. This prospective meta-analysis pooled data from 7 randomized controlled trials of corticosteroid therapy in 1703 critically ill patients hospitalized with COVID-19. Similar to findings from the RECOVERY trial, corticosteroids were associated with lower all-cause mortality at 28 days after randomization, and this benefit was observed both in critically ill patients who were receiving mechanical ventilation or supplemental oxygen without mechanical ventilation. Interestingly, while the OR estimates were imprecise, the reduction in mortality rates was similar between patients who were administered dexamethasone and hydrocortisone, which may suggest a general drug class effect. In addition, the mortality benefit of corticosteroids appeared similar for those aged ≤ 60 years and those aged > 60 years, between female and male patients, and those who were symptomatic for ≤ 7 days or > 7 days before randomization. Moreover, the administration of corticosteroids did not appear to increase the risk of SAEs. While more data are needed, results from the RECOVERY trial and this prospective meta-analysis indicate that corticosteroids should be an essential pharmacologic treatment for COVID-19, and suggest its potential role as a standard of care for critically ill patients with COVID-19.
This study has several limitations. First, not all trials systematically identified participated in the meta-analysis. Second, long-term outcomes after hospital discharge were not captured, and thus the effect of corticosteroids on long-term mortality and other adverse outcomes, such as hospital readmission, remain unknown. Third, because children were excluded from study participation, the effect of corticosteroids on pediatric COVID-19 patients is unknown. Fourth, the RECOVERY trial contributed more than 50% of patients in the current analysis, although there was little inconsistency in the effects of corticosteroids on mortality between individual trials. Last, the meta-analysis was unable to establish the optimal dose or duration of corticosteroid intervention in critically ill COVID-19 patients, or determine its efficacy in patients with mild-to-moderate COVID-19, all of which are key clinical questions that will need to be addressed with further clinical investigations.
The development of effective treatments for COVID-19 is critical to mitigating the devastating consequences of SARS-CoV-2 infection. Several recent COVID-19 clinical trials have shown promise in this endeavor. For instance, the Adaptive COVID-19 Treatment Trial (ACCT-1) found that intravenous remdesivir, as compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.6 Moreover, there is some evidence to suggest that convalescent plasma and aerosol inhalation of IFN-κ may have beneficial effects in treating COVID-19.7,8 Thus, clinical trials designed to investigate combination therapy approaches including corticosteroids, remdesivir, convalescent plasma, and others are urgently needed to help identify interventions that most effectively treat COVID-19.
Applications for Clinical Practice
The use of corticosteroids in critically ill patients with COVID-19 reduces overall mortality. This treatment is inexpensive and available in most care settings, including low-resource regions, and provides hope for better outcomes in the COVID-19 pandemic.
Katerina Oikonomou, MD, PhD
General Hospital of Larissa, Larissa, Greece
Fred Ko, MD, MS
Study Overview
Objective. To assess the association between administration of systemic corticosteroids, compared with usual care or placebo, and 28-day all-cause mortality in critically ill patients with coronavirus disease 2019 (COVID-19).
Design. Prospective meta-analysis with data from 7 randomized clinical trials conducted in 12 countries.
Setting and participants. This prospective meta-analysis included randomized clinical trials conducted between February 26, 2020, and June 9, 2020, that examined the clinical efficacy of administration of corticosteroids in hospitalized COVID-19 patients who were critically ill. Trials were systematically identified from ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the EU Clinical Trials Register, using the search terms COVID-19, corticosteroids, and steroids. Additional trials were identified by experts from the WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Senior investigators of these identified trials were asked to participate in weekly calls to develop a protocol for the prospective meta-analysis.1 Subsequently, trials that had randomly assigned critically ill patients to receive corticosteroids versus usual care or placebo were invited to participate in this meta-analysis. Data were pooled from patients recruited to the participating trials through June 9, 2020, and aggregated in overall and in predefined subgroups.
Main outcome measures. The primary outcome was all-cause mortality up to 30 days after randomization. Because 5 of the included trials reported mortality at 28 days after randomization, the primary outcome was reported as 28-day all-cause mortality. The secondary outcome was serious adverse events (SAEs). The authors also gathered data on the demographic and clinical characteristics of patients, the number of patients lost to follow-up, and outcomes according to intervention group, overall, and in subgroups (ie, patients receiving invasive mechanical ventilation or vasoactive medication; age ≤ 60 years or > 60 years [the median across trials]; sex [male or female]; and the duration patients were symptomatic [≤ 7 days or > 7 days]). For each trial, the risk of bias was assessed independently by 4 investigators using the Cochrane Risk of Bias Assessment Tool for the overall effects of corticosteroids on mortality and SAEs and the effect of assignment and allocated interventions. Inconsistency between trial results was evaluated using the I2 statistic. The trials were classified according to the corticosteroids used in the intervention group and the dose administered using a priori-defined cutoffs (15 mg/day of dexamethasone, 400 mg/day of hydrocortisone, and 1 mg/kg/day of methylprednisolone). The primary analysis utilized was an inverse variance-weighted fixed-effect meta-analysis of odds ratios (ORs) for overall mortality. Random-effects meta-analyses with Paule-Mandel estimate of heterogeneity were also performed.
Main results. Seven trials (DEXA-COVID 19, CoDEX, RECOVERY, CAPE COVID, COVID STEROID, REMAP-CAP, and Steroids-SARI) were included in the final meta-analysis. The enrolled patients were from Australia, Brazil, Canada, China, Denmark, France, Ireland, the Netherlands, New Zealand, Spain, the United Kingdom, and the United States. The date of final follow-up was July 6, 2020. The corticosteroids groups included dexamethasone at low (6 mg/day orally or intravenously [IV]) and high (20 mg/day IV) doses; low-dose hydrocortisone (200 mg/day IV or 50 mg every 6 hr IV); and high-dose methylprednisolone (40 mg every 12 hr IV). In total, 1703 patients were randomized, with 678 assigned to the corticosteroids group and 1025 to the usual-care or placebo group. The median age of patients was 60 years (interquartile range, 52-68 years), and 29% were women. The larger number of patients in the usual-care/placebo group was a result of the 1:2 randomization (corticosteroids versus usual care or placebo) in the RECOVERY trial, which contributed 59.1% of patients included in this prospective meta-analysis. The majority of patients were receiving invasive mechanical ventilation at randomization (1559 patients). The administration of adjunctive treatments, such as azithromycin or antiviral agents, varied among the trials. The risk of bias was determined as low for 6 of the 7 mortality results.
A total of 222 of 678 patients in the corticosteroids group died, and 425 of 1025 patients in the usual care or placebo group died. The summary OR was 0.66 (95% confidence interval [CI], 0.53-0.82; P < 0.001) based on a fixed-effect meta-analysis, and 0.70 (95% CI, 0.48-1.01; P = 0.053) based on the random-effects meta-analysis, for 28-day all-cause mortality comparing all corticosteroids with usual care or placebo. There was little inconsistency between trial results (I2 = 15.6%; P = 0.31). The fixed-effect summary OR for the association with 28-day all-cause mortality was 0.64 (95% CI, 0.50-0.82; P < 0.001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths); the OR was 0.69 (95% CI, 0.43-1.12; P = 0.13) for hydrocortisone (3 trials, 374 patients, and 94 deaths); and the OR was 0.91 (95% CI, 0.29-2.87; P = 0.87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Moreover, in trials that administered low-dose corticosteroids, the overall fixed-effect OR for 28-day all-cause mortality was 0.61 (95% CI, 0.48-0.78; P < 0.001). In the subgroup analysis, the overall fixed-effect OR was 0.69 (95% CI, 0.55-0.86) in patients who were receiving invasive mechanical ventilation at randomization, and the OR was 0.41 (95% CI, 0.19-0.88) in patients who were not receiving invasive mechanical ventilation at randomization.
Six trials (all except the RECOVERY trial) reported SAEs, with 64 events occurring among 354 patients assigned to the corticosteroids group and 80 SAEs occurring among 342 patients assigned to the usual-care or placebo group. There was no suggestion that the risk of SAEs was higher in patients who were administered corticosteroids.
Conclusion. The administration of systemic corticosteroids was associated with a lower 28-day all-cause mortality in critically ill patients with COVID-19 compared to those who received usual care or placebo.
Commentary
Corticosteroids are anti-inflammatory and vasoconstrictive medications that have long been used in intensive care units for the treatment of acute respiratory distress syndrome and septic shock. However, the therapeutic role of corticosteroids for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was uncertain at the outset of the COVID-19 pandemic due to concerns that this class of medications may cause an impaired immune response in the setting of a life-threatening SARS-CoV-2 infection. Evidence supporting this notion included prior studies showing that corticosteroid therapy was associated with delayed viral clearance of Middle East respiratory syndrome or a higher viral load of SARS-CoV.2,3 The uncertainty surrounding the therapeutic use of corticosteroids in treating COVID-19 led to a simultaneous global effort to conduct randomized controlled trials to urgently examine this important clinical question. The open-label Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial, conducted in the UK, was the first large-scale randomized clinical trial that reported the clinical benefit of corticosteroids in treating patients hospitalized with COVID-19. Specifically, it showed that low-dose dexamethasone (6 mg/day) administered orally or IV for up to 10 days resulted in a 2.8% absolute reduction in 28-day mortality, with the greatest benefit, an absolute risk reduction of 12.1%, conferred to patients who were receiving invasive mechanical ventilation at the time of randomization.4 In response to these findings, the National Institutes of Health COVID-19 Treatment Guidelines Panel recommended the use of dexamethasone in patients with COVID-19 who are on mechanical ventilation or who require supplemental oxygen, and recommended against the use of dexamethasone for those not requiring supplemental oxygen.5
The meta-analysis discussed in this commentary, conducted by the WHO REACT Working Group, has replicated initial findings from the RECOVERY trial. This prospective meta-analysis pooled data from 7 randomized controlled trials of corticosteroid therapy in 1703 critically ill patients hospitalized with COVID-19. Similar to findings from the RECOVERY trial, corticosteroids were associated with lower all-cause mortality at 28 days after randomization, and this benefit was observed both in critically ill patients who were receiving mechanical ventilation or supplemental oxygen without mechanical ventilation. Interestingly, while the OR estimates were imprecise, the reduction in mortality rates was similar between patients who were administered dexamethasone and hydrocortisone, which may suggest a general drug class effect. In addition, the mortality benefit of corticosteroids appeared similar for those aged ≤ 60 years and those aged > 60 years, between female and male patients, and those who were symptomatic for ≤ 7 days or > 7 days before randomization. Moreover, the administration of corticosteroids did not appear to increase the risk of SAEs. While more data are needed, results from the RECOVERY trial and this prospective meta-analysis indicate that corticosteroids should be an essential pharmacologic treatment for COVID-19, and suggest its potential role as a standard of care for critically ill patients with COVID-19.
This study has several limitations. First, not all trials systematically identified participated in the meta-analysis. Second, long-term outcomes after hospital discharge were not captured, and thus the effect of corticosteroids on long-term mortality and other adverse outcomes, such as hospital readmission, remain unknown. Third, because children were excluded from study participation, the effect of corticosteroids on pediatric COVID-19 patients is unknown. Fourth, the RECOVERY trial contributed more than 50% of patients in the current analysis, although there was little inconsistency in the effects of corticosteroids on mortality between individual trials. Last, the meta-analysis was unable to establish the optimal dose or duration of corticosteroid intervention in critically ill COVID-19 patients, or determine its efficacy in patients with mild-to-moderate COVID-19, all of which are key clinical questions that will need to be addressed with further clinical investigations.
The development of effective treatments for COVID-19 is critical to mitigating the devastating consequences of SARS-CoV-2 infection. Several recent COVID-19 clinical trials have shown promise in this endeavor. For instance, the Adaptive COVID-19 Treatment Trial (ACCT-1) found that intravenous remdesivir, as compared to placebo, significantly shortened time to recovery in adult patients hospitalized with COVID-19 who had evidence of lower respiratory tract infection.6 Moreover, there is some evidence to suggest that convalescent plasma and aerosol inhalation of IFN-κ may have beneficial effects in treating COVID-19.7,8 Thus, clinical trials designed to investigate combination therapy approaches including corticosteroids, remdesivir, convalescent plasma, and others are urgently needed to help identify interventions that most effectively treat COVID-19.
Applications for Clinical Practice
The use of corticosteroids in critically ill patients with COVID-19 reduces overall mortality. This treatment is inexpensive and available in most care settings, including low-resource regions, and provides hope for better outcomes in the COVID-19 pandemic.
Katerina Oikonomou, MD, PhD
General Hospital of Larissa, Larissa, Greece
Fred Ko, MD, MS
1. Sterne JAC, Diaz J, Villar J, et al. Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials. Trials. 2020;21:734.
2. Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31:304-309.
3. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for citically Ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197:757-767.
4. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19 - preliminary report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020;NEJMoa2021436.
5. NIH COVID-19 Treatment Guidelines. National Institutes of Health. www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/. Accessed September 11, 2020.
6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19--preliminary report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;NEJMoa2007764.
7. Casadevall A, Joyner MJ, Pirofski LA. A randomized trial of convalescent plasma for covid-19-potentially hopeful signals. JAMA. 2020;324:455-457.
8. Fu W, Liu Y, Xia L, et al. A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19. EClinicalMedicine. 2020;25:100478.
1. Sterne JAC, Diaz J, Villar J, et al. Corticosteroid therapy for critically ill patients with COVID-19: A structured summary of a study protocol for a prospective meta-analysis of randomized trials. Trials. 2020;21:734.
2. Lee N, Allen Chan KC, Hui DS, et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol. 2004;31:304-309.
3. Arabi YM, Mandourah Y, Al-Hameed F, et al. Corticosteroid therapy for citically Ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med. 2018;197:757-767.
4. RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19 - preliminary report [published online ahead of print, 2020 Jul 17]. N Engl J Med. 2020;NEJMoa2021436.
5. NIH COVID-19 Treatment Guidelines. National Institutes of Health. www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/. Accessed September 11, 2020.
6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19--preliminary report [published online ahead of print, 2020 May 22]. N Engl J Med. 2020;NEJMoa2007764.
7. Casadevall A, Joyner MJ, Pirofski LA. A randomized trial of convalescent plasma for covid-19-potentially hopeful signals. JAMA. 2020;324:455-457.
8. Fu W, Liu Y, Xia L, et al. A clinical pilot study on the safety and efficacy of aerosol inhalation treatment of IFN-κ plus TFF2 in patients with moderate COVID-19. EClinicalMedicine. 2020;25:100478.